Polyethylene particles of a 'critical size' are necessary for the induction of cytokines by macrophages in vitro

Particulate wear debris from total hip prosthetic components can stimulate macrophages to produce mediators of osteolysis which may cause aseptic impl ant loosening. This study evaluated the in vitro response of murine periton eal macrophages to polyethylene particles of difinitive size distributions at varying volume doses. Ceridust 3615 polyethylene particles with a mean s ize of 0.21, 0.49, 4.3 and 7.2 mu m and GUR1120 polyethylene resin with a m ean size of 88 mu m were co-cultured with C3H murine peritoneal macrophages at volume (mu m)(3) to cell number ratios of 100:1, 10:1, 1:1 and 0.1:1. T he secretion of IL-6, IL-1 beta and TNF-alpha was determined by ELISA. Sign ificantly elevated levels of TNF-alpha and IL-1 beta were determined at 100 :1 ratios when the macrophages were challenged with particles with a mean s ize of 0.49, 4.3 and 7.2 mu m, and at 10:1 ratios for particles with a mean size of 0.49 and 4.3 mu m. IL-6 production was significantly elevated at 1 00:1 ratios for mean particle sizes of 0.49 and 4.3 mu m. Particles outside this range produced considerably less cytokine suggesting that both the si ze and volume (or number) of polyethylene particles are critical factors in macrophage activation. Therefore particles in the phagocytosable size rang e of 0.3-10 mu m appear to be the most biologically active. (C) 1998 Publis hed by Elsevier Science Ltd. All rights reserved.